Although viruses are the causative agents of a number of human and animal diseases, there is currently a paucity of antiviral agents effective in ablating or minimizing virus infection in these hosts. Vaccines have been successfully developed which protect humans against infection by only a few viruses including measles, rubella, mumps, hepatitis A, hepatitis B, influenza and poliomyelitis viruses. However, vaccination has little or no effect in individuals who are infected prior to vaccination. In addition, there are as yet no effective vaccines for the prevention of many viral infections including infection by Human Immunodeficiency Virus (HIV). There is therefore a long felt need for the development of agents for treatment of viral infections in general and in particular, for treatment of those viral infections for which there are no available vaccines.
Traditionally, the most successful approach to the discovery of new antiviral agents has been the empirical screening of large numbers of chemically diverse classes of compounds and natural products for their ability to inhibit virus replication (Johnston et al., 1993, Science 260:1286-1293; van der Sijs et al., 1994, Int. J. Biochem. 26:621-630). Antiviral agents which have been discovered in traditional cell culture screening assays include 3'-azidothymidine (AZT), 2',3'-dideoxyinosine (ddI) and 2',3'-dideoxycytidine (DDC). However, the empirical screening process is usually tedious and inefficient. Additional approaches to the development of antiviral agents such as rational drug design based on the known structures of viral or cellular proteins are promising but have to date had limited success.
The present invention provides a novel and rapid method for screening of compounds for activity in inhibiting infection by infectious agents, which method has significant advantages over conventional screening techniques. Compounds which are generated using the methods of the invention also have significant advantages over currently available anti-infectious agent compositions and in particular antiviral compositions.